This research project proposes to study the control of cellular calcium metabolism in cultured kidney cells and in rat kidney slices. The importance of mitochondrial calcium transport in the control of the cytosolic free calcium which regulates many cellular functions will be investigated. The ionic and endocrine regulation of intracellular calcium metabolism and transport will be studied, in particular the role of parathyroid hormone, cyclic AMP, calcitonin, hydrogen ion and phosphate. The following techniques will be used: chemical determination of calcium in cellular and subcellular fractions, the kinetic analysis of 45Ca uptake and desaturation curves, computer analysis and simulation of the experimental data. An attempt will be made to develop a method to monitor changes in intracellular free calcium by incorporation into cells a phosphoprotein (aequorin) which emits light in proportion to the levels of free calcium. These studies are designed to better understand the metabolism of intracellular calcium which is one of the most important regulators of many cell functions; cell mitosis and cell growth, cellular communication, secretion, contraction, motility, transmission of nerve impulses, and renal or intestinal calcium transport. Clinically these studies many elucidate some aspects of the pathology of calcium metabolism in hyper-and hypoparathyroidism. Sections of the proposal dealing with the hyperparathyroidism, produced by high phosphate diets may be relevant to two diseases which afflict a majority of the population: osteoporosis and peridontal disease.